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International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pertinent for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/). The majority of the data were from HIV/HBV coinfected cohorts. The commonest RAM was rtM204I/V, either alone or in combination with associated mutations, and identified in both reportedly treatment-naïve and treatment-experienced adults. We also identified the suite of mutations rtM204V/I + rtL180M + rtV173L, that has been associated with vaccine escape, in over 1/3 of cohorts. Although tenofovir has a high genetic barrier to resistance, it is of concern that emerging data suggest polymorphisms that may be associated with resistance, although the precise clinical impact of these is unknown. Overall, there is an urgent need for improved diagnostic screening, enhanced laboratory assessment of HBV before and during therapy, and sustained roll out of tenofovir in preference to lamivudine alone. Further data are needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in these highly vulnerable settings.

Increased clinical and scientific scrutiny is being applied to hepatitis B virus (HBV), with focus on the development of new therapeutic approaches, ultimately aiming for cure. Defining the optimum natural CD8+ T cell immune responses that arise in HBV, mediated by HLA class I epitope presentation, may help to inform novel immunotherapeutic strategies. Therefore, we have set out to develop a comprehensive database of these epitopes in HBV, coined ‘Hepitopes’. This undertaking has its foundations in a systematic literature review to identify the sites and sequences of all published class I epitopes in HBV. We also collected information regarding the methods used to define each epitope, and any reported associations between an immune response to this epitope and disease outcome. The results of this search have been collated into a new open-access interactive database that is available at http://www.expmedndm.ox.ac.uk/hepitopes . Over time, we will continue to refine and update this resource, as well as inviting contributions from others in the field to support its development. This unique new database is an important foundation for ongoing investigations into the nature and impact of the CD8+ T cell response to HBV.

International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pertinent for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (

International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pressing for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/). The majority of the data were from HIV/HBV coinfected cohorts. The commonest RAM was rtM204I/V, either alone or in combination with compensatory mutations, and reported in both treatment-naive and treatment-experienced adults. We also identified the suite of mutations rtM204V/I + rtL180M + rtV173L that is reported in association with vaccine escape, in over 1/3 of cohorts. Although tenofovir has a high genetic barrier to drug resistance, it is of concern that emerging data suggest polymorphisms that may be associated with resistance, although the precise impact of these is unknown. Overall, there is an urgent need for improved diagnostic screening, enhanced laboratory assessment of HBV before and during therapy, and sustained roll out of tenofovir in preference to lamividine. Further data are urgently needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in these highly vulnerable settings.

Although it takes several hundred milliseconds to prepare a spoken contribution, gaps between turns in conversation tend to be much shorter. To produce these short gaps, it appears that interlocutors predict the end of their partner's turn. The theory of prediction-by-simulation proposes that individuals use their own motor system to model a partner's upcoming actions by referring to prior production experience. In this study we investigate the role of motor experience for both predicting a turn-end and producing a spoken response by manipulating the similarity of heard speech to participants' own production style. We hypothesised that they would be better at predicting, and initiating responses to, speech produced in the style they speak themselves. Participants recorded a series of questions in two sessions, and several months later they listened to their own speech and that of a stylistically similar and a stylistically dissimilar participant (as assessed by independent raters). Participants predicted the end of 60 of these questions by pressing a button, and for the remaining 60 questions, by producing a spoken response. An analysis of response times showed that participants' button-press responses were faster for utterances spoken by themselves and by a stylistically similar partner, than for utterances spoken by a stylistically dissimilar partner. We conclude that simulation facilitates prediction of similar speakers.

Background Over the past decade, assessments of surgical capacity in low- and middle-income countries (LMICs) have contributed to our understanding of barriers to the delivery of surgical services in a number of countries. It is yet unclear, however, how the findings of these assessments have been applied and built upon within the published literature. Methods A systematic literature review of surgical capacity assessments in LMICs was performed to evaluate current levels of understanding of global surgical capacity and to identify areas for future study. A reverse snowballing method was then used to follow-up citations of the identified studies to assess how this research has been applied and built upon in the literature. Results Twenty-one papers reporting the findings of surgical capacity assessments conducted in 17 different LMICs in South Asia, East Asia and Pacific, Latin America and the Caribbean, and sub-Saharan Africa were identified. These studies documented substantial deficits in human resources, infrastructure, equipment, and supplies. Only seven additional papers were identified which applied or built upon the studies. Among these, capacity assessment findings were most commonly used to develop novel tools and intervention strategies, but they were also used as baseline measurements against which updated capacity assessments were compared. Conclusions While the global surgery community has made tremendous progress in establishing baseline values of surgical capacity in LMICs around the world, further work is necessary to build upon and apply the foundational knowledge established through these efforts. Capacity assessment data should be coordinated and used in ongoing research efforts to monitor and evaluate progress in global surgery and to develop targeted intervention strategies. Intervention strategy development may also be further incorporated into the evaluation process itself.

Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases. Whether mucinous ovarian carcinoma (MOC) arises from cells at the ovary or from metastases from other primary sites is an unanswered question. Here, Cheasley et al perform a genetic analysis of the disease, showing that MOC arises at the ovary.

Hyper-Kamiokande will be a next-generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this paper, the physics potential of a long-baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis uses the framework and systematic uncertainties derived from the ongoing T2K experiment. With a total exposure of 7.5 MW $\\times 10^7$s integrated proton beam power (corresponding to $1.56 \\times 10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5^\\circ$ off-axis neutrino beam, it is expected that the leptonic $CP$ phase $\\delta _{CP}$ can be determined to better than 19 degrees for all possible values of $\\delta _{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\\,\\sigma$ ($5\\,\\sigma$) for $76{\\%}$ ($58{\\%}$) of the ${\\delta _{CP}}$ parameter space. Using both $\\nu _e$ appearance and $\\nu _\\mu$ disappearance data, the expected 1$\\sigma$ uncertainty of $\\sin ^2\\theta _{23}$ is 0.015(0.006) for $\\sin ^2\\theta _{23}=0.5(0.45)$.

Successful duetting requires that musicians coordinate their performance with theft partners. In the case of turn-taking in improvised performance they need to be able to predict their partners turn-end in order to accurately time their own entries. Here we investigate the cues used for accurate turn-end prediction in musical improvisations, focusing on the role of tonal structure. In a response-time task, participants more accurately determined the endings of (tonal) jazz than (non-tonal) free improvisation turns. Moreover, for the jazz improvisations, removing low frequency information (c 2100 Hz) - and hence obscuring the pitch relationships conveying tonality - reduced response accuracy, but removing high frequency information (> 2100 Hz) had no effect. Neither form of filtering affected response accuracy in the free improvisation condition. We therefore argue that tonal cues aided prediction accuracy for the jazz improvisations compared to the free improvisations. We compare our results with those from related speech research (De Ruiter et al., 2006), to draw comparisons between the structural function of tonality and linguistic syntax.

There is a need for an accurate non-invasive diagnostic test for variant Creutzfeldt-Jakob disease (vCJD). We investigated the sensitivity and specificity of bilateral pulvinar high signal on magnetic resonance imaging (MRI) for the diagnosis of vCJD. MRI from patients with vCJD and controls (patients with suspected CJD) were analysed. Scans were reviewed on two separate occasions by two neuroradiologists and scored for the distribution of changes, and likely final diagnosis. Scans from vCJD cases were reassessed to reach a consensus on all abnormalities. We analysed 36 patients and 57 controls. vCJD patients were correctly identified based on bilateral pulvinar high signal in 29 of 36 and 32 of 36 cases on the first assessment by the two radiologists, and 32 of 36 and 31 of 36 on their second assessment. Bilateral increased pulvinar signal was identified in one of 57 and one of 57 controls on the first assessment and two of 57 and three of 57 controls on the second assessment. These reported changes in controls were graded as minimal/equivocal in six of seven patients and moderate in one (<0·5% of all control assessments). 80% of the assessments in vCJD cases were graded as moderate or substantial. On consensus review, 28 of 36 cases and none of 57 controls had prominent bilateral pulvinar signal—sensitivity 78% (95% CL 60–90%) and specificity 100% (95% CI 94–100%). Other common MRI features of vCJD were medial thalamic and periaqueductal grey matter high signal, and the notable absence of cerebral atrophy. Pulvinar high signal correlated with histological gliosis. In the appropriate clinical context the MRI identification of bilaterally increased pulvinar signal is a useful non-invasive test for the diagnosis of vCJD.